The candidate proposes a career development Pathway to Independence Award to further advance her laboratory and clinical research skills in the area of symptom science research. Each aim of the proposal is supported by didactic coursework, research training experiences, scientific meetings and seminars, and a detailed dissemination plan. The candidate?s ultimate career goal is to become an independent, extramurally-funded nurse scientist with expertise in biological underpinnings of cancer-related fatigue (CRF), one of the most commonly reported side effects of cancer and its treatment. The etiology of CRF is poorly understood and there is no clear, single, clinical definition. The purpose of this proposal is to identify cellular stress response genes that define a unique external beam radiation therapy (EBRT)-related fatigue phenotype. The K99 period of the proposal will focus on identifying a cluster of cellular stress response genes from the peripheral blood cells of men who are at risk to develop acute clinically-significant fatigue during EBRT for non-metastatic prostate cancer (NM-PC) and validating the functional role of these differentially expressed genes in cellular energy production using an in vitro radiation-induced cell stress model. The R00 period will identify a cluster of cell stress response genes from peripheral blood cells of men who are at risk to develop persistent clinically-significant fatigue months after completion of EBRT for NM-PC and to identify genes at EBRT completion that can serve as prognostic markers of persistent fatigue. Questionnaire data assessing CRF and peripheral blood samples for genetic analysis will be collected during EBRT and following EBRT completion. The overall goal of this K99/R00 research proposal is to provide the candidate with expertise in advancing symptom science through the performance and interpretation of genetic assays under the guidance of an experienced team of scientists. The findings from the K99/R00 investigations will optimize precision medicine in oncology by identifying prognostic genetic markers that can define a unique EBRT-related fatigue phenotype, as well as identify biologically-relevant therapeutic targets to manage EBRT-related fatigue.